Related Experiment Video
Updated: Jan 3, 2026
Detrusor Underactivity Model in Rats by Conus Medullaris Transection
Published on: August 28, 2020
New targets for overactive bladder-ICI-RS 2109
Christopher Henry Fry1, Basu Chakrabarty1, Hikaru Hashitani2
1School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
Aim:
To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms.
Methods:
A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB.
Results:
Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide-dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1 , TRPV4 , TRPA1 , and TRPM4 ) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+ -activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway-the canonical fibrosis pathway.
Conclusions:
The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
Insights
Novel drug targets for overactive bladder (OAB) focus on bladder wall tissues and the storage phase of the micturition cycle. Research reviews pathways like cyclic nucleotides, beta-3 agonists, TRP channels, and antifibrosis agents for OAB management.
Area of Science:
- Pharmacology
- Urology
- Cell Biology
Background:
- Overactive bladder (OAB) significantly impacts quality of life.
- Current OAB treatments have limitations, necessitating novel therapeutic strategies.
- Identifying specific drug targets within the bladder wall is crucial for effective OAB management.
Purpose of the Study:
- To review existing evidence for novel drug targets for managing overactive bladder (OAB) symptoms.
- To propose new drug targets in the urinary bladder for OAB treatment based on literature and expert experience.
Main Methods:
- A think tank approach was employed, synthesizing literature evidence and research experience.
- Five key classes of agents or cellular pathways were evaluated for their potential in OAB treatment.
- Considered pathways include cyclic nucleotide signaling, novel beta-3 agonist targets, TRP channels, calcium-activated potassium channels, and antifibrosis agents targeting TGF-beta.
Main Results:
- Cyclic nucleotide pathways (cAMP, cGMP) influencing ATP release from nerves and urothelium were examined.
- Novel targets for beta-3 agonists, including bladder vasculature and muscularis mucosa, were identified.
- Several TRP channels (TRPV1, TRPV4, TRPA1, TRPM4) and small conductance Ca2+-activated K+ channels were implicated in detrusor overactivity and spontaneous contractions.
Conclusions:
- Specificity of drug action is a key consideration due to widespread distribution of target receptors/pathways.
- Further research is needed to detail OAB pathophysiology and direct drug specificity to bladder changes.
- Future targets should focus on the storage phase of the micturition cycle and encompass the entire bladder wall, not solely the detrusor muscle.
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